The primary purpose of the proposed study is the relationship between folic acid and vitamin B12. The specific objectives are: 1) to study the mechanism whereby methionine influences the metabolism of Figlu, formate and glycine. The effect of B12 and methionine on the uptake of tritiated folic acid by various tissues and on the proportion of 5-CH3-FH4 to FH4 will be studied. 2) To study the synthesis of folic acid polyglutamates in liver. It has been reported that in E. coli polyglutamates can be made only from FH4 but not from 5-CH3-FH4. If this is true in mammalian tissue it could explain the effect of methionine and B12 in increasing polyglutamate levels (and thereby total folate levels) in liver, since methionine increases the proportion of FH4. Polyglutamate synthetase in liver will be purified and the role of various folic acid substrates determined. 3) The effect of nitrosamines (DEN) on folic acid metabolism. The feeding of nitrosamines increases the excretion of Figlu which can be corrected by feeding methionine but not by folic acid or B12. Studies will be made with the objective of identifying the site of the action of DEN. 4) Determination of the availability of folic acid in foods and a study of factors in foods which influence folic acid absorption from the intestine. This could include the effect of anticonvulsants and of oral contraceptives on folate absorption during the latter half of the grant period.